Approximately one percent of all newborn humans have evidence of congenital heart defects, many of which have been linked to defects in specific developmental events. Despite the medical importance of understanding heart development, little is known of the molecular bases for the cellular processes that drive development from one stage to the next. Heart development involves a well-characterized series of morphological changes. Specific molecules involved in cell-cell adhesion (CAMs) and cell-substratum adhesion (SAMs) have been demonstrated to regulate morphogenesis in other systems and are correlated with other developmentally-important primary processes such as cell migration, programmed cell death, and cytodifferentiation; more-over, although several of these CAMs and SAMs have been detected in the developing heart, little is known of their modulatory behavior in this organ. Therefore, an understanding of cell-cell and sell-substrate adhesion is likely to be crucial to understanding the constant remolding of tissues that is typical of cardiac morphogenesis. Our goal is to determine how the expression of specific molecules mediating cell adhesion is involved in the control of heart development. Specifically, we propose to: 1) use immunohistochemical methods to correlate the expression of CAMs and SAMs in the developing heart with morphological changes, 2) use biochemical methods to identify developmental changes in the levels and molecular forms of CAMs and SAMs that have been shown to modulate their function in other systems, 3) demonstrate using functional assays in vitro that CAMs and SAMs are indeed involved in cell-cell and cell-matrix adhesion and developmentally-related processes in the heart, and 4) directly investigate the role of these molecules in development in vivo by determining the ability of antibodies to these molecules to inhibit heart development in cultured embryos and by examining the distribution of these molecules in a developmental mutant defective in the laterality of certain cardiac structures. Such studies will begin to elucidate the interrelationship between adhesion and other processes leading to heart morphogenesis.